BI513 Nervous System Flashcards
1
Q
What are the 3 classifications of neurons and what do they do?
A
1) Afferent neurons - carry info to CNS
2) Interneurons - integrate info in CNS
3) Efferent neurons - carry info away from CNS
2
Q
What are the two types of glial cells in the PNS and what are their functions?
A
1) Schwaan Cells - produce myelin
- secrete neurotrophic factors e.g nerve growth factor
2) Satellite Cells - support cell bodies in ganglia
Note: ganglia are clusters of cell bodies outside the CNS
3
Q
What are the 4 types of glial cells in the CNS and what are their functions?
A
1) Oligodendrocytes - produce myelin
2) Microglia - Macrophage type cells that protect the nerve cells
3) Astrocytes
- secrete neurotrophic factors
- take up neurotransmitters (essential to prevent continued action)
- surround the capillaries that form the blood-brain barrier which regulates movement of substances between blood and brain
- provide neurons with substances for ATP synthesis
4) Ependymal cells
- forms a layer of epithelial cells (the ependyma), that lines the ventricles of the brain and the central canal of the spinal cord
- some act as stem cells that can differentiate into neurons and glia
4
Q
How much of the axon does each Schwaan cell myelinate?
A
~ 1-1.5 mm
5
Q
How many layers of myelin can an axon be wrapped in?
A
up to 150
6
Q
What is white matter?
A
Areas of the CNS that contain high numbers of myelinated axons
7
Q
What is grey matter?
A
Areas of the CNS that contain a high number of cell bodies, dendrites and unmyelinated axons
8
Q
What are the 3 types of channels in neuronal membranes?
A
1) Voltage gated
2) Chemical gated
3) Mechanically gated
9
Q
What are the characteristics of graded potentials
A
- size of depolarisation or hyperpolarisation is directly proportional to signal strength
- usually occurs at dendrites and cell bodies
- two signals arriving close together may sum to produce a larger response
- if graded potentials are large enough (suprathreshold) they will initiate an action potential
- potentials lose strength with distance from site of initiation
10
Q
What are the characteristics of an action potential?
A
- All or nothing law
- strength and duration of stimulus represented by frequency of action potentials
- usually occur at axon hillock
- no summation due to refractory period
- permit rapid signalling over long distances
11
Q
Explain how an action potential occurs
A
1) Resting membrane potential (-70mV)
2) Depolarising stimulus
3) Membrane depolarises to threshold
Voltage gated Na+ channels open
4) Na+ entry further depolarises membrane
5) Voltage gated K+ channels open (+30mV)
6) K+ leaves the cell
Membrane returns to resting potential
7) Cell hyperpolarises due to loss of K+ (-90mV)
8) Voltage gated channels close
9) Resting membrane potential restored by Na+/K+ pump
12
Q
How does an action potential move along an axon?
A
Positive charge created flows into adjacent region of the axon by local current flow
13
Q
What 2 physiological factors affect the speed of conduction?
A
1) Axon diameter
- larger diameter + faster speed as less resistance to current flow
2) Myelination
- Saltatory conduction can occur in myelinated axons
- conduction slowed in demyelinated axons
14
Q
How do myelinated axons allow faster conduction?
A
Current flows from one node of Ranvier to the next through insulated regions of axon which are resistant to current leak
15
Q
How fast do myelinated and unmyelinated axons conduct?
A
Myelinated - 120m/sec
Unmyelinated - 2m/sec
16
Q
What are the 2 types of synapses and briefly explain each type
A
1) Electrical - electric current passes directly from pre to post synaptic neuron through gap junction
2) Chemical - chemical signal eg neurotransmitter
17
Q
What are gap junctions and that are they composed of?
A
- Intercellular channels formed by the docking of 2 hemichannels
- Hemichannels composed of 6 connexins or innexin proteins
18
Q
What are the 4 stages of chemical transmission?
A
1) Neurotransmitter release
2) Storage/Release
3) Receptor binding
4) Inactivation
19
Q
What are the 3 types of classical neurotransmitters and give examples
A
1) Acetylcholine (ACH)
2) Biogenic amines
- noradrenline
- dopamine
- serotonin
- histamine
3) Amino acids
- glutamate
- gamma-aminobutyric acid (GABA)
- glycine
20
Q
What are the 2 types of peptide neurotransmitters
A
- Substance P
- Opioids (endorphins, enkephalins)
21
Q
What are the 3 types of unconventional transmitters and give examples
A
Gases: nitric oxide
Purines: adenosine triphosphate (ATP)
Lipids: cannabinoids
22
Q
How are neurons named?
A
Neurotransmitter + ‘ergic’
e.g cholinergic neurons secrete ACH
noradrenergic secrete noradrenaline
23
Q
Explain how ACH is synthesised?
A
- synthesised in the nerve terminal
- choline taken from plasma
- acetyl-CoA derived from glucose metabolism in mitochondria
- choline acetyltransferase catalyses transfer of acetyl group from acetyl-CoA to make acetylcholine
- Vesicular acetylcholine transporter (VACHT) loads acetylcholine into vesicles
24
Q
Explain how ACH is degraded
A
- Degraded by acetylcholinesterase found in extracellular space and postsynaptic membrane
- Broken down into acetic acid and choline
25
What are constitutive and regulated exocytosis?
Constitutive - constant flow of material out of the membrane
| Regulated - material only moved when triggered by other factor
26
Outline the mechanism of neurotransmitter release
11) Action potential depolarises the nerve terminal
2) Voltage gated Ca2+ channels open
Ca2+ moves into presynaptic cell by diffusion
3) Ca2+ binds to regulatory proteins on synaptic vesicle membrane and triggers the vesicle to fuse with the PM, releasing neurotransmitter
4) Neurotransmitter binds to receptors on post synaptic membrane, exciting or inhibiting the post synaptic cell
27
What are the 2 main types of neurotransmitter receptors?
1) Ionotrophic - transmitter binding opens an ion cchannel
| 2) Metabotrophic/G protein coupled - transmitter binding changes concentration of intracellular metabolites e.g CAMP
28
By what 2 methods are neurotrasmitters removed from the synaptic cleft?
1) Enzyme degradation in synaptic cleft
| 2) Re-uptake into nerve terminal or glia followed by enzyme metabolism
29
How are ACH, biogenic amines and amino acids removed?
- ACH broken down by acetylcholinesterase in synaptic cleft
- Biogenic amines taken into nerve terminal
- Amino acids taken into nerve terminal and glia
30
What are the outermost protective layers of the CNS and what are their structures?
Cranium and vertebral column
- Cranial bones interconnected by immovable fibrous joints
- Vertebrae (7 cervical, 12 thoracic, 5 lumbar, 5 fused sacral and 4 fused coccyx) separated by intervertebral disks that permit limited movement
- nerves of the PNS enter and leave spinal cord through spaces in stacked vertebrae
31
What protects the CNS between the bone and the nerves?
Meninges
- protective membranes between the bone and the nervous tissue
- Dura mater: outer, next to bone
- Arachnoid membrane: middle
- Pia matar: inner, next to nerves
- subarachnoid space between arachnoid membrane and pia mater contains cerebrospinal fluid (CSF)
32
What is the total volume of the fluid compartments of the brain and what does it consist of?
Internal volume of cranium ~ 1.4 L = 1L cells and 0.4L fluid
- 100-150ml blood
- cerebrospinal fluid: in brain ventricles and subarachnoid space
- interstitial fluid: inside pia matar
33
What are the characteristics of CSF
- produced by the choroid plexus
- filtrate of blood that contains no blood cells, vvery little protein and different ionic composition (similar Na+, less K+, Ca2+, HCO-)
- absorbed back into blood by villi on arachnoid membrane
34
What are the characteristics of the choroid plexus
- lines the ventricles
- consists of transporting epithelia and capillaries
- filters blood, removing cells, most protein and some other solutes
35
Why is the blood brain barrier necessary?
- 15% of the total blood pumped from heart (1L/min) goes to the brain
- Neurons require high oxygen levels and glucose to make ATP for active transport BUT must be protected from toxins and harmful substances
36
Describe the structure of the blood-brain barrier
- Specialised selectively permeable capillaries
- Capillary endothelial cells have tight junctions and use membrane transporters to move nutrients from blood to brain
- Astrocyte foot processes surround the capillaries and secrete molecules that induce tight junction formation
37
What are the 3 main regions of the CNS
1) Cerebrum - large, folded
2) Cerebellum - second largest region of brain, sits under cerebrum
3) Brain stem and spinal cord
38
Test on brain regions and diagram in notes
.
39
Describe the ascending and descending tracts of the spinal cord
Ascending - sensory info from spinal cord to brain
| Descending - motor info from brain to spinal cord
40
Where do sensory neurons enter the SC and motor neurons leave the SC
Sensory neurons - have cell bodies in dorsal root ganglion, enter the dorsal side of the SC
Motor neurons - have cell bodies in the ventral horn, leave the SC in the ventral root
41
What are the 2 types of efferent neurons?
1) Somatic motor: to skeletal muscle to control posture and movement
2) Autonomic: innervate smooth and cardiac muscle
42
What neurotransmitter and receptor is used in the somatic motor pathway?
ACH and nicotinic ACH receptor
43
What is a motor unit?
a motor neuron and all the muscle fibres it innervates
44
Where do sympathetic and parasympathetic neurons originate from?
Sympathetic - thoracic and lumbar regions of SC
| Parasympathetic - brain stem or sacral region of the SC
45
For the sympathetic nervous system, what neurotransmitter and receptor is used for both the pre and postganglionic neuron.
Pre: ACH and nicotinic ACH receptor
Post: Noradrenaline and adrenergic receptor
46
For the parasympathetic nervous system, what neurotransmitter and receptor is used for both the pre and postganglionic neuron.
Pre: ACH and nicotinic ACH receptor
Post: ACH and muscarinic ACH receptor
47
Describe the structure of nerve terminals that innervate smooth muscle
Axons end with a series of varicosities, each containing synaptic vesicles
Neurotransmitter released diffusely over the muscle fibres
48
What are the main 2 neurodegenerative diseases
Alzheimer's disease
| Parkinson's disease
49
What are the 3 main demyelinating diseases?
Multiple sclerosis
Guillain-Barré syndrome
Charcot-Marie-Tooth Disease
50
What are the 2 main disorders of neurotransmitter systems?
Myasthenic disorders: neuromuscular junction
| Depression
51
When was alzheimer's first described?
1907
52
How much of the world population is affected by Alzheimer's and how many people is this
~0.5% of the worlds population
| ~ 35 million people
53
What % of people over 65 and 80 have Alzheimer's?
over 65: 7-10%
| over 80: 40%
54
What are the symptoms of Alzheimer's disease?
Cognitive impairment:
- Loss of memory
- Inability to communicate
55
What causes Alzheimer's
Degeneration of cholinergic neurons of the forebrain
56
What does the brain of an Alzheimer's patient look like?
Surface of brain shows enlarged sulci (grooves) and reduced gyri (folds) due to neuronal loss
57
What are amyloid plaques?
extracellular deposits of degenerating nerve processes and a core of insoluble beta-amyloid protein
58
What are Neurofibrillary tangles?
NFTs are found in neuronal cell bodies and axons and are composed of a hyperphosphorylated form of the microtubule associated protein tau that aggregates into paired helical filament
59
What are the genetic factors that cause Alzheimer's?
Mutations in the genes encoding amyloid precursor protein (APP) and presenilin among others
60
What is the environmental factor thought to contribute to Alzheimer's disease?
high soil levels of aluminium
61
How do APP and Presenilin mutations lead to formation of amyloid plaques?
- Amyloid precursor protein is a membrane protein normally found in neurons
- Secretase enzymes (alpha, beta and gamma secretase) cleave APP into fragments
- Presenilin is necessary for gamma-secretase activity
- Some fragments such as p3 are harmless
- AB fragments, particularly AB42, are toxic to neurons
- Amount of toxic AB42 increases when APP or presenilin are mutated
62
What is the only current treatment for Alzheimer's?
Acetylcholinesterase inhibitors or ACH receptor agonists that mimic ACH alleviate symptoms in some patients
63
What are the 4 possible future treatments for Alzheimer's?
- Secretase inhibitors to prevent formation of amyloid plaques or agents to dissolve plaques
- Antibody based drugs designed to target toxic AB
- Vaccine to improve immunity to toxic AB
- Stem cells to replace lost neurons
63
When was Parkinson's first described?
1817
64
What % of the worlds population is affected by Parkinson's?
0.2%
65
What are the symptoms of Parkinson's?
Tremor of the limbs
Difficulty initiating movement
Abnormal gait-walking like a shuffling run ("festination")
Jerky movements due to rigidity around joints ("cogwheeling")
66
What is Parkinson's caused by?
Degeneration in dopaminergic neurons of the nigrostriatal pathway that controls movement
67
What is the nigrostiatal pathway?
Neurons that project from the substantia nigra to the striatum
68
What causes dopaminergic neurons to degenerate?
dense deposits called Lewy bodies
69
What environmental factors cause Parkinson's?
- MPTP is oxidised by the enzyme monoamine oxidase found in dopaminergic neurons and in glia, to MPP+ which inhibits mitochondria function killing the cell
- Exposure to pyridine compounds in herbicides and pesticides may cause or increase the risk of Parkinson's
70
What 2 gene mutations cause Parkinson's?
1) SNCA gene that encodes the protein alpha-synuclein
2) PARK2 gene that encodes the protein parkin
- Alpha-synuclein is a nerve terminal protein
- Parkin is an enzyme component of the ubiquitin-proteasome pathway responsible for removal of damaged or excess protein
- Gene mutations lead to Lewy Bodies, the main component of which is a toxic form of alpha-synuclein
71
What are the 2 main current treatments for Parkinson's and give examples for each
1) Drugs
- L-DOPA, the precursor of dopamine, acts to restore brain dopamine levels
- Inhibitors of enzyme monoamine oxidase which degrades dopamine
2) Deep brain stimulation
- surgical procedure; electrodes implanted to override the abnormal electrical impulses
72
Name a potential future treatment
Cell replacement by stem cells
73
What % of the population suffer from MS?
~0.04%
| - Over 1% in Northern Europe, North America, Australia and New Zealand
74
When does diagnosis usually occur?
Between 20-40
75
What causes MS?
Lesions, progressing to sclerosis, form in the myelin sheath of the CNS, leading to inflammation and loss of myelin
76
What are some symptoms of MS?
Difficulty walking
Visual problems
Fatigue
77
Name the 4 types of MS and give a description of each
1) Relapsing Remitting MS (RRMS)
- ~80% of patients in early phase of disease
- altering periods of illness and recovery, no marked degradation over time
2) Secondary Progressive MS (SPMS)
- high % of RRMS patients develop SPMS ~10 years after onset
- Progressive neurological deterioration, fewer remissions, incomplete recovery
3) Progressive Relapsing MS (PRMS)
- ~5% of patients
- alternating periods of relapse and remission but progressive deterioration between relapses
4) Primary Progressive (PPMS)
~ 10-15% of patients
- progressive from onset - no remissions
78
Other than genetics, what other 2 reasons are suggested for causing MS?
1) Infectious agent
- Focus on Epstein Barr but others too e.g measles, herpes, chlamydia
2) Immune-mediated
- Antibodies produced attack myelin sheath
- May involve molecular mimicry - normal protein resembles foreign substance so is attacked
79
What gene complex is associated with contributing to MS?
Major histocompatibility complex (MHC)
80
Name the 4 methods used to diagnose MS
- 'Hot bath test' - raising body temp slows conduction in demyelinated plaques, amplifying symptoms
- Nerve conduction test
- Sampling of CSF by lumbar puncture for presence of white blood cells or antibodies
- MRI to look for abnormalities in white matter
81
What are the 2 treatments for MS?
- Drugs such as beta-interferons
| - Exercise, physio, diet
82
What is Guillian-Barre Syndrome and when was it first described
- Autoimmune demyelinating disease
| - 1916
83
What is the prevalence of this disease?
1-2 in 100,000
84
What are the symptoms of the disease and which neurons cause each one?
General peripheral neuropathy affecting:
- somatic motor neurons (paralysis, respiratory problems)
- sensory neurons (loss of sensation)
- autonomic neurons (fluctuating blood pressure, cardiac arrhythmia's)
85
What causes GB syndrome?
Antibodies, triggered by viral infection or immunisation, attack components of Schwaan cell myelin
86
What are the 2 treatments for GB syndrome?
- Immunoglobulins administered intravenously
| - Plasmapheresis (plasma exchange)
87
What is Charcot-Marie-Tooth Disease (CMT) and when was it first described?
- Inherited demyelinating disease
| - 1880s
88
What are the symptoms of CMT disease?
Peripheral motor and sensory neuropathy
- weakness of leg, foot and hand muscles (motor)
- reduced ability to perceive pain, temp etc (sensory)
89
How common is CMT disease?
1 in 2500
90
How is CMT disease inherited?
- ~ 80-90% is autosomal (dominant or recessive)
| - remainder are X linked (CMTX)
91
What is Connexin 32 and what is its role in CMT disease?
- Found in Schwaan cells and forms gap junctions between layers of myelin membranes surrounding peripheral axons
- Gap junctions provide route for transfer of nutrients through the myelin to inner myelin layers
- Cx332 loff of function mutations lead to degredation of inner myelin and the axon
92
What are the symptoms of Myasthenic disorders?
- Muscular weakness
| - Fatigability affecting ocular, facial, respiratory and limb muscles
93
Are myasthenic disorders autoimmune or genetic?
Both
94
What is the prevalence of Myasthenia Gravis?
15-20 in 100,000
95
What causes Myasthenia Gravis?
Auto antibodies attack protein subunits of the nicotinic ACH receptor
- antibodies either block transmitter binding, increase rate of receptor degradation or destroy post synaptic membrane resulting in cell lysis
96
What causes Lambert-Eaton Myathenia (LEMs)
- auto antibodies attack voltage gated Ca2+ channels in the motor neuron presynaptic terminal, reducing ACH release
(may be associated with lung or other cancers)
97
What causes Congenital Myasthenia Syndromes (CMS)?
mutations in gene for nicotinic ACH receptor subunits causing ACH receptor deficiency
98
What causes Congenital Myasthenia Syndrome with Episodic Apnea (CMSEA)
- mutations in choline acetyltransferase, less ACH produced
99
What causes End Plate Acetylcholinesterase Deficiency?
Mutations in acetylcholinesterase, overstimulation of skeletal muscle
100
What % of the worlds population suffer from depression?
10%
101
What are some symptoms of depression?
- Alterations in mood
- Inability to sleep
- Changes in appetite
102
What is Endogenous Depression?
- Arises without any identifiable cause
| - Very likely to have a genetic basis
103
What is Exogenous Depression?
- Associated with a stressful lifestyle
104
What are the 2 subdivisions of both endogenous and exogenous depression?
- Monopolar (major depression) and Bipolar (manic depression)
105
What happens to neurotransmitters during depression?
- Associated with imbalances in activity of central monoaminergic and cholinergic pathways of limbic system
- lower than normal activity at synapses using monoamine transmitters; noradrenaline, dopamine and serotonin
- relative over activity at cholinergic synapses
106
Is depression a single gene or multiple gene disorder?
Multiple
107
What is the major treatment for depression and give examples
Drug treatments aim to elevate levels of monoamine transmitters at the synapse:
- tricyclic antidepressants (eg amitriptyline) block reuptake of noradrenaline
- selective seretonin reuptake inhibitors (SSRI's eg Prozac/Fluoxetine)
- monoamine oxidase (MAO) inhibitors prevent breakdown of monoamine transmitters
